Patent EA-002763-B1 (EA)
Title: Alpha-aminoamide useful as analgetic agents
Inventor: PEVARELLO PAOLO
IPC: C07C255/54
Filed: 1998-12-12
Abstract: 1. Use, in the manufacture of a medicament for use as an analgesic, of a compound which is an alpha-aminoamide of formula (I)   wherein: A is a - (CH2)m-, - (CH2)n-X- or - (CH2)v-O- group wherein m is an integer of 1 to 4, n is zero or an integer of 1 to 4, X is -S- or -NH-, and v is zero or an integer of 1 to 5; s is 1 or 2; R is a furyl, thienyl, or pyridyl ring or a phenyl ring optionally substituted by one or two substitutents independently chosen from halogen, cyano, C1-C4 alkyl, C1-C4 alkoxy and trifluoromethyl; R1 is hydrogen or C1-C4 alkyl; one of R2 and R3 is hydrogen and the other is hydrogen or C1-C4 alkyl optionally substituted by hydroxy or phenyl; or R2 and R3 taken together with the carbon atom to which they are linked form a C3-C6 cycloalkyl ring; or R2 and R3 are both methyl; R4 is hydrogen or C1-C4 alkyl ring; or a pharmaceutically acceptable salt thereof; with the provisos that, when A is a -(CH2)5-O- group then s is 1, R is a phenyl group optionally substituted by one or two substitutents selected independently from halogen, trifluoromethyl and C1-C4 alkoxy, R1 is hydrogen and one of R2 and R3 is hydrogen and the other is hydrogen or C1-C4 alkyl optionally substituted hydroxy; and when R2 and R3 are both methyl then R is other than a furyl, thienyl or pyridyl ring. 2. Use according to claim 1, wherein the medicament is for the treatment or alleviation of chronic or neuropathic pain. 3. Use according to claim 1, wherein, in formula (I) A is a group chosen from -CH2-, -CH2-CH2-, -CH2-S-, -CH2-CH2-S- and - (CH2)v-O- in which v is an integer of 1 to 5; s is 1 or 2; R is a phenyl ring optionally substituted by one or two substitutents independently chosen from halogen and cyano or a thienyl ring; R1 is hydrogen or C1-C4 alkyl; one of R2 and R3 is hydrogen and the other is C1-C4 alkyl optionally substituted by hydroxy or phenyl; or R2 and R3 are both methyl; and R4 is hydrogen or C1-C4 alkyl. 4. Use according to claim 1, wherein the compound is selected from: 2-[4-(3-fluorobenzyloxy)benzylamino]-2-methyl-propanamide; 2-[4-(3-fluorobenzyloxy)benzylamino]propanamide; 2-(4-benzyloxybenzylamino)propanamide; 2-[4-(2-fluorobenzyloxy)benzylamino]propanamide; 2-[4-(4-fluorobenzyloxy)benzylamino]propanamide; 2-[4-(2-chlorobenzyloxy)benzylamino]propanamide; 2-[4-(3-chlorobenzyloxy)benzylamino]propanamide; 2-[4-(3-fluorobenzyloxy)benzylamino]-3-hydroxy-N-methylpropanamide; 2-[4-(2-fluorobenzyloxy)benzylamino]-3-hydroxy-N-methylpropanamide; 2-[4-(2-chlorobenzyloxy)benzylamino]-3-hydroxy-N-methylpropanamide; 2-[4-(3-cyanobenzyloxy)benzylamino]-3-hydroxy-N-methylpropanamide; 2-[4-(3-chlorobenzyloxy)phenylethylamino]-propanamide; 2-(4-benzyloxybenzylamino)-3-hydroxy-N-methyl-propanamide; 2-(4-(2-thenyloxy)benzylamino)-propanamide; 2-[4-(3-fluorobenzyloxy)benzylamino)-N-methylpropanamide; 2-[4-(3-fluorobenzyloxy)benzylamino]-3-hydroxy-propanamide; 2-[4-(2-(3-fluorophenyl)ethyloxy)benzylamino)-propanamide; 2-[4-(2-(3-fluorophenyl)ethyl)benzylamino]-propanamide; 2-[N-4-benzyloxybenzyl-N-methyl-amino]-propanamide; 2-[2-(4-(3-chlorobenzyloxy)phenylethyl)amino]-propanamide; 2-[4-benzylthiobenzylamino]-propanamide; 2-[4-(3-phenylpropyloxy)benzylamino]-propanamide; 2-[4-(4-phenylbutyloxy)benzylamino]-propanamide; 2-[4-(5-phenylpentyloxy)benzylamino]-propanamide; 2-[4-benzyloxybenzylamino]-3-phenyl-N-methylpropanamide; 2-[4-benzyloxybenzylamino]-3-methyl-N-methylbutanamide, if the case either as a single isomer or as a mixture thereof, or a pharmaceutically acceptable salt thereof. 5. A pharmaceutical composition having analgesic activity, comprising a pharmaceutically acceptable excipient and, as an active agent, a compound as defined in claim 1. 6. A method of treating a mammal, including a human, in need of an analgesic agent, said method comprising administering thereto an effective amount of a compound of formula (I), as defined in claim 1, or a pharmaceutically acceptable salt thereof. 7. A compound which is an alpha-aminoamide of formula (IA)   wherein: A is a - (CH2)m- or - (CH2)n-E- group wherein m is an integer of 1 to 4, n is zero or an integer of 1 to 4 and E is O-, -S- or -NH-; s is 1 or 2; one of R10 and R11 is cyano and the other is independently selected from hydrogen, halogen, cyano, C1-C4 alkyl, C1-C4 alkoxy and trifluoromethyl; R1 is hydrogen or C1-C4 alkyl; one of R2 and R3 is hydrogen and the other is hydrogen or C1-C4 alkyl optionally substituted by hydroxy or phenyl; or R2 and R3 taken together with the carbon atom to which they are linked forth a C3-C6 cycloalkyl ring; or R2 and R3 are both methyl; R4 is hydrogen or C1-C4 alkyl ring; or a pharmaceutically acceptable salt thereof. 8. A compound according to claim 7, wherein A is a group -CH2-O- or -CH2-CH2-O-, s is l; one of R10 and R11 is cyano and the other is hydrogen, cyano or halogen; and one of R2 and R3 is hydrogen and the other is C1-C4 alkyl optionally substituted by hydroxy; or R2 and R3 are both methyl. 9. A compound selected from: 2-[4-(3-cyanobenzyloxy)benzylamino]-3-hydroxy-N-methylpropanamide;and [2-[4-(3-cyanobenzyloxy)benzyl]-2-methyl-amino]-3-hydroxy-N-methyl-propanamide, if the case either as a single isomer or as a mixture thereof, and the pharmaceutically acceptable salts thereof. 10. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and, as an active agent, a compound as defined in claim 7. 11. A compound as defined in claim 7 for use as in a method of treatment of the human or animal body by therapy. 12. A compound as claimed in claim 11 for use as an analgesic agent.